SYSTEMATIC REVIEW article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1567111
This article is part of the Research TopicVaccines and Molecular Therapeutics for TuberculosisView all 7 articles
Immune mechanisms mediating the heterologous effects of BCG vaccination: a systematic review
Provisionally accepted
- 1University of Oxford, Oxford, England, United Kingdom
- 2Germans Trias i Pujol Health Science Research Institute (IGTP), Barcelona, Catalonia, Spain
- 3Department of Biology, Mathematical, Physical and Life Sciences Division, University of Oxford, Oxford, United Kingdom
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BCG vaccination can have heterologous or non-specific effects (NSE) that confer resistance against pathogens other than its target Mycobacterium tuberculosis, but the underlying mechanisms are not fully understood. We conducted a systematic review synthesizing existing literature on immune mechanisms mediating the heterologous/NSE of BCG. Searches were conducted using MEDLINE and Scopus, and 1032 original records were identified, of which 67 were deemed eligible. Several potentially relevant immune pathways were identified, although there may be variation by pathogen. Recent studies have focused on trained immunity whereby innate cells, or the hematopoietic stem and progenitor cells from which they are derived, undergo epigenetic and metabolic reprogramming allowing them to respond more effectively to antigen exposures unrelated to the original stimulus. However, other processes such as granulopoiesis and cross-reactive adaptive immunity may also play a role. Heterologous immunity and NSEs may be influenced by several endogenous and exogenous variables. We discuss the quality of available data, the importance of understanding mechanisms of heterologous protection, and its implications for vaccination strategies.
Keywords: BCG, heterologous effects of vaccination, trained immunity, T cells, humoral immunity
Received: 26 Jan 2025; Accepted: 28 Apr 2025.
Copyright: © 2025 Torracinta, Gogichadze and Tanner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Rachel Tanner, Department of Biology, Mathematical, Physical and Life Sciences Division, University of Oxford, Oxford, United Kingdom
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